Long-term effects of lateral hypothalamic lesions on brown adipose tissue in rats

Abstract

A classic feature of animals with lateral hypothalamic (LH) lesions is their regulation of body weight at sub-normal levels. The present studies were done to determine whether this is associated with enhanced thermogenic activity of their brown adipose tissue (BAT). Three groups of young chow-fed male Holtzman rats were formed: (1) animals receiving bilateral radiofrequency heat lesions of the dorsal LH and then permitted free access to chow (LH rats); (2) non-lesioned animals that were pair-fed (PF) to the lesioned rats during a 2 week post-operative recovery period (Phase 1); (3) non-lesioned, ad lib fed (NORM) controls. After Phase 1, each group was divided and permitted free access to chow alone or an additional selection of palatable, novel food items (a “cafeteria” diet) for 2–3 weeks (Phase 2) to stimulate diet-induced thermogenesis in BAT. Finally, half of each sub-group was exposed to 4°C for 15 hr to stimulate nonshivering thermogenesis in BAT. During Phase 1 LHs and PFs ate 50% less than NORMs. This resulted in a weight deficit of 16% for LHs and 12% for PFs. After the additional period of feeding palatable foods (Phase 2) LHs collectively weighed 14% less than NORMs whereas previously PFs had a weight deficit of only 4%. They gained less weight than NORMs or PFs despite a similar energy intake. LHs had small deposits of gonadal white adipose tissue [both total amount and expressed per metabolic body mass (kg 0.75)]. The weight of interscapular BAT was less in the LHs but its concentration of protein (mg/g) was higher. Total protein in BAT was normal but expressed in terms of metabolic body mass (kg 0.75) was significantly greater in the LHs. LHs grew more BAT protein in response to the cafeteria diet than did NORMs or PFs. The thermogenic state of BAT (as indicated by mitochondrial GDP binding) tended to be slightly higher in the LHs. Normal increases in GDP binding in response to the cafeteria diet and to cold-exposure occurred in the LHs. It is concluded that LH-lesioned rats have more BAT relative to their body size than do normal or previously pair-fed rats, are capable of normal cold-induced nonshivering thermogenesis in BAT and exhibit an exaggerated dietinduced growth of BAT. The LH lesion appears to prevent the atrophy of BAT and suppression of thermogenesis in BAT that would be expected to occur as a response to reduced food intake.